Methods for producing transgenic mice using retroviral vectors (Non-Patent Document 1) are known as methods for introducing genes at the individual level using viral vectors. Transgenic mice can be efficiently produced by using retroviral vectors; however, a disadvantage is that silencing of gene expression occurs as a result of methylation of introduced genes, or the like (Non-Patent Document 2).
Long term expression of introduced genes can be expected with the lentivirus vector which is a retroviral vector, because it enables integration of foreign genes into chromosome. Furthermore, unlike typical retroviral vectors, lentivirus vectors have a nuclear translocation signal, and thus can introduce genes into non-dividing cells. When transgenic mice are produced using lentivirus vectors, the efficiency of production increases and gene silencing does not occur in long-term gene expression (Non-Patent Documents 3 to 5).
In these methods of transgenic mouse production, genes are introduced into most viral vector-infected fertilized eggs. Furthermore, these methods introduce genes into both placenta and embryo, and thus are regarded as very excellent techniques in developmental studies.
[Non-Patent Document 1] Proc. Natl. Acad. Sci. USA., 1985, September; 82(18): 6148-6152
[Non-Patent Document 2] Proc. Natl. Acad. Sci. USA., 1985, October; 82(20): 6927-6931
[Non-Patent Document 3] Mol. Cell. Biol., 2000, October; 20(20): 7419-7426
[Non-Patent Document 4] J. Virol., 2000, November; 74(22): 10778-10784
[Non-Patent Document 5] Proc. Natl. Acad. Sci. USA., 2002, Feb. 19; 99(4): 2140-2145